E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Colo-Rectal Cancer |
Cancer ColoRectal |
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E.1.1.1 | Medical condition in easily understood language |
Colo-Rectal Cancer |
Cancer ColoRectal |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052362 |
E.1.2 | Term | Metastatic colorectal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061451 |
E.1.2 | Term | Colorectal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Determine the rate of objective response at two months for colorectal liver metastases receiving optimized and targeted delivery of systemic chemotherapy combining bevacizumab and FOLFIRI based on US waves and gaseous microbubbles in colorectal liver metastases compared with those treated with only systemic chemotherapy regimen. |
Déterminer le pourcentage de réponse objective à 2 mois des métastases hépatiques après délivrance ciblée de bevacizumab et FOLFIRI par US et microbulles comparativement à celles traitées uniquement par bevacizumab et FOLFIRI en systémique. |
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E.2.2 | Secondary objectives of the trial |
- Safety and tolerability based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (semi quantitative score) until D60 - Percent reduction in tumor density on CT scan and MRI from baseline - Assessment of tumor vascularity on CT scan and MRI from baseline - Assessment of tumor vascularity with Dynamic Contrast-Enhanced US (DCE-US) - Biological parameters: dosages and kinetic of bevacizumab and cytokines |
- Évaluer la tolérance du protocole (selon les critères CTCAE du NCI) durant les 3 mois de suivi (score semi quantitatif) - Évaluer la nécrose de la métastase - Évaluer la vascularisation métastatique - Pharmacocinétique du bevacizumab et évolution des profils sanguins de cytokines |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- patient with non resectable liver metastases from colorectal cancer; patient with minimum two liver metastases which satisfy all the following criteria: diameter between 10 and 35 mm; arterially enhancing liver metastases detected with contrast enhanced ultrasound (CEUS); measurable liver metastases with CT-scan - age ≥ 18 years; - ECOG/OMS 0-1; - life expectancy of at least 12 weeks; - adequate bone marrow, liver and kidney function; - written informed consent obtained from subject; - subjects covered by or having the rights to social security. |
- Ayant au minimum 2 métastases hépatiques non résécables de CCR (ø 10-35 mm ; réhaussement artériel objectivé à l’échographie de contraste ; métastase visible et mesurable au TDM) - Âge ≥ 18 ans - Score 0 ou 1 sur l’Échelle de Zubrod ECOG/OMS - Espérance de vie > 12 semaines - Pas d’anomalie des fonctions rénale, hépatique, et de la moelle osseuse - Consentement éclairé écrit - Affiliation à un régime de sécurité sociale |
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E.4 | Principal exclusion criteria |
- Previous systemic or local treatment of liver metastases; - neo-adjuvant or adjuvant chemotherapy/radiotherapy in the 6 months prior to entering the study; - patient with resectable liver metastasis and no contraindication to hepatic resection; - indication for local ablative therapy (radiofrequency ablation or other validated hepatic-directed modality of treatment); - known contraindication to the injection of Sonovue®, of Gadolinium, of iodated contrast agent; - contraindication to MRI or perfusion CT scan; - Patient under legal protection; - Pregnant or lactating woman, or woman with ability to procreate and without contraception; - Inclusion in another therapeutic assay |
- Métastases hépatiques déjà traitées (traitement systémique ou local) - Chimiothérapie néo ou adjuvante / Radiothérapie < 6 mois - Métastases résécables et pas de contre-indication à la résection hépatique - Indication pour une ablation locale (RadioFréquences ou autres techniques validées) - Contre-indication au SonoVue®, au Gadolinium, aux produits de contraste iodés - Contre-indication à l’IRM ou TDM - Sujet sous protection -Femme enceinte, allaitante ou en capacité de procréer et sans contraception -Inclusion dans un autre essai thérapeutique |
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E.5 End points |
E.5.1 | Primary end point(s) |
The objective response will be determined for each selected liver metastasis with spiral CT scan and defined as a decrease of at least 30% in the longest diameter of each selected liver metastases. |
La réponse sera déterminée par la diminution d’au moins 30% du plus grand diamètre de chaque métastase hépatique évaluée au scanner. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Safety and tolerability based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (semi quantitative score) until D60 - Percent reduction in tumor density on CT scan and MRI from baseline - Assessment of tumor vascularity on CT scan and MRI from baseline - Assessment of tumor vascularity with Dynamic Contrast-Enhanced US (DCE-US) - Biological parameters: dosages and kinetic of bevacizumab and cytokines |
- Evaluation de la sécurité et de la tolérance basée sur le CTCAE (Common Terminology Criteria for Adverse Events) du NCI (National Cancer Institute) jusqu’à J60 - Pourcentage de réduction de la densité au scanner et à l’IRM par rapport à la baseline - Évaluer la vascularisation métastatique au scanner et à l’IRM par rapport à la baseline - Évaluer la vascularisation métastatique avec l’Echographie de Contraste (CEUS) grâce aux paramètres standards de perfusion - Paramètres biologiques : dosages et cinétique du bevacizumab et des cytokines |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- 2 months - 2 months - 2 months - 2 months - end of the follow-up |
- 2 mois - 2 mois - 2 mois - 2 mois - fin du suivi |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
absence de traitement complémentaire |
no complementary treatment |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |